An approach for prevention planning based on the prevalence and comorbidity of neurodevelopmental disorders in 6-year-old children receiving primary care consultations on the island of Menorca.

BACKGROUND: Few studies have estimated the real prevalence of neurodevelopmental disorders according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) in Spain and worldwide. However, there are disparate prevalence figures. We consider research in this field essential to improve early detection, secondary prevention, and health planning. METHODS: The Minikid ADHD and TICS-Mini International Neuropsychiatric Interview for Children and Adolescents, the Autism Spectrum Quotient (Children's version, AQ- Child) and a protocol of general medical questions were administered for screening purposes. The PROLEXIA battery for children aged from 4 to 6 years was used for direct assessments. Parents provided information on emotional, medical, and school aspects. The final population evaluated using these tools consisted of 291 6-year-old subjects. RESULTS: The overall risk of presenting with a neurodevelopmental disorder was 55.4%. A 23.4% risk of presenting with attention-deficit/hyperactivity disorder (ADHD) in any modality (inattentive, hyperactive-impulsive and combined), a 2.8% risk of developing autism spectrum disorder (ASD), a 30.6% risk of presenting with a learning disorder with reading difficulties, a 5.5% risk of tics and a 22.5% risk of language problems (incomprehensible language or minor language problems) were detected in the sample. The most common combination of disorders was learning and language difficulties, accounting for 6.9% of the sample. The second most frequent combination was the presence of learning and language difficulties and ADHD, accounting for 4.5% of the sample. CONCLUSIONS: The prevalence of risks detected in our sample seems to be consistent with national and international studies. A significant proportion of our sample had never been previously diagnosed (85%), so early detection programs are recommended.

Emotion processing in maltreated boys and girls: Evidence for latent vulnerability.

Evidence of alterations in emotion processing in maltreated youth has been hypothesized to reflect latent vulnerability for psychopathology. However, previous studies have not systematically examined the influence of psychopathology on the results. Here, we examined emotion recognition and learning in youth who differed in terms of presence vs. absence of maltreatment and psychopathology and tested for potential sex effects. Maltreatment and psychopathology were assessed in 828 youth (514 females) aged 9-18 years using diagnostic interviews and self- and parent-report questionnaires. Emotion recognition was assessed via identification of morphed facial expressions of six universal emotions. For emotion learning, reward and punishment values were assigned to novel stimuli and participants had to learn to correctly respond/withhold response to stimuli to maximize points. A three-way interaction of maltreatment by psychopathology by emotion indicated that when psychopathology was low, maltreated youth were less accurate than non-maltreated youth for happy, fear and disgust. A three-way interaction of sex, maltreatment and emotion indicated that maltreated girls and boys were impaired for fear, but girls showed an impairment for happy, while boys for disgust. There were no effects of maltreatment, psychopathology, or sex on reward learning. However, a two-way interaction between sex and maltreatment showed that maltreated girls were worse at learning from punishment relative to non-maltreated girls, while maltreated boys were better than non-maltreated boys. The study provides the first clear evidence of latent-vulnerability in emotion recognition in maltreated youth and suggests that girls and boys might be characterized by distinct profiles of emotion recognition and learning following maltreatment.

Machine learning classification of conduct disorder with high versus low levels of callous-unemotional traits based on facial emotion recognition abilities.

Conduct disorder (CD) with high levels of callous-unemotional traits (CD/HCU) has been theoretically linked to specific difficulties with fear and sadness recognition, in contrast to CD with low levels of callous-unemotional traits (CD/LCU). However, experimental evidence for this distinction is mixed, and it is unclear whether these difficulties are a reliable marker of CD/HCU compared to CD/LCU. In a large sample (N = 1263, 9-18 years), we combined univariate analyses and machine learning classifiers to investigate whether CD/HCU is associated with disproportionate difficulties with fear and sadness recognition over other emotions, and whether such difficulties are a reliable individual-level marker of CD/HCU. We observed similar emotion recognition abilities in CD/HCU and CD/LCU. The CD/HCU group underperformed relative to typically developing (TD) youths, but difficulties were not specific to fear or sadness. Classifiers did not distinguish between youths with CD/HCU versus CD/LCU (52% accuracy), although youths with CD/HCU and CD/LCU were reliably distinguished from TD youths (64% and 60%, respectively). In the subset of classifiers that performed well for youths with CD/HCU, fear and sadness were the most relevant emotions for distinguishing them from youths with CD/LCU and TD youths, respectively. We conclude that non-specific emotion recognition difficulties are common in CD/HCU, but are not reliable individual-level markers of CD/HCU versus CD/LCU. These findings highlight that a reduced ability to recognise facial expressions of distress should not be assumed to be a core feature of CD/HCU.

A Phase III Study of Bumetanide Oral Liquid Formulation for the Treatment of Children and Adolescents Aged Between 7 and 17 Years with Autism Spectrum Disorder (SIGN 1 Trial): Participant Baseline Characteristics.

The efficacy of bumetanide (oral liquid formulation 0.5 mg bid) as a treatment for the core symptoms of autism spectrum disorders in children and adolescents aged 7-17 years is being investigated in an international, randomised, double-blind, placebo-controlled phase III study. The primary endpoint is the change in Childhood Autism Rating Scale 2 (CARS2) total raw score after 6 months of treatment. At baseline, the 211 participants analysed are broadly representative of autistic subjects in this age range: mean (SD) age, 10.4 (3.0) years; 82.5% male; 47.7% with intelligence quotient ≥ 70. Mean CARS2 score was 40.1 (4.9) and mean Social Responsiveness Scale score was 116.7 (23.4). Final study results will provide data on efficacy and safety of bumetanide in autistic children and adolescents.

Sex differences in psychiatric comorbidity and clinical presentation in youths with conduct disorder.

BACKGROUND: Conduct disorder (CD) rarely occurs alone but is typically accompanied by comorbid psychiatric disorders, which complicates the clinical presentation and treatment of affected youths. The aim of this study was to investigate sex differences in comorbidity pattern in CD and to systematically explore the 'gender paradox' and 'delayed-onset pathway' hypotheses of female CD. METHODS: As part of the FemNAT-CD multisite study, semistructured clinical interviews and rating scales were used to perform a comprehensive phenotypic characterization of 454 girls and 295 boys with CD (9-18 years), compared to 864 sex- and age-matched typically developing controls. RESULTS: Girls with CD exhibited higher rates of current major depression, anxiety disorders, post-traumatic stress disorder and borderline personality disorder, whereas boys with CD had higher rates of current attention-deficit/hyperactivity disorder. In line with the 'gender paradox' hypothesis, relative to boys, girls with CD showed significantly more lifetime psychiatric comorbidities (incl. Alcohol Use Disorder), which were accompanied by more severe CD symptoms. Female and male youths with CD also differed significantly in their CD symptom profiles and distribution of age-of-onset subtypes of CD (i.e. fewer girls with childhood-onset CD). In line with the 'delayed-onset pathway' hypothesis, girls with adolescent-onset CD showed similar levels of dimensional psychopathology like boys with childhood-onset CD, while boys with adolescent-onset CD had the lowest levels of internalizing psychopathology. CONCLUSIONS: Within the largest study of CD in girls performed to date, we found compelling evidence for sex differences in comorbidity patterns and clinical presentation of CD. Our findings further support aspects of the 'gender paradox' and 'delayed-onset pathway' hypotheses by showing that girls with CD had higher rates of comorbid lifetime mental disorders and functional impairments, and they usually developed CD during adolescence. These novel data on sex-specific clinical profiles of CD will be critical in informing intervention and prevention programmes.

Positive and negative parenting in conduct disorder with high versus low levels of callous-unemotional traits.

Less is known about the relationship between conduct disorder (CD), callous-unemotional (CU) traits, and positive and negative parenting in youth compared to early childhood. We combined traditional univariate analyses with a novel machine learning classifier (Angle-based Generalized Matrix Learning Vector Quantization) to classify youth (N = 756; 9-18 years) into typically developing (TD) or CD groups with or without elevated CU traits (CD/HCU, CD/LCU, respectively) using youth- and parent-reports of parenting behavior. At the group level, both CD/HCU and CD/LCU were associated with high negative and low positive parenting relative to TD. However, only positive parenting differed between the CD/HCU and CD/LCU groups. In classification analyses, performance was best when distinguishing CD/HCU from TD groups and poorest when distinguishing CD/HCU from CD/LCU groups. Positive and negative parenting were both relevant when distinguishing CD/HCU from TD, negative parenting was most relevant when distinguishing between CD/LCU and TD, and positive parenting was most relevant when distinguishing CD/HCU from CD/LCU groups. These findings suggest that while positive parenting distinguishes between CD/HCU and CD/LCU, negative parenting is associated with both CD subtypes. These results highlight the importance of considering multiple parenting behaviors in CD with varying levels of CU traits in late childhood/adolescence.

ESCAP practice guidance for autism: a summary of evidence-based recommendations for diagnosis and treatment.

Across Europe, there is increased awareness of the frequency and importance of autism spectrum disorder (ASD), which is now recognised not only as a childhood disorder but as a heterogeneous, neurodevelopmental condition that persists throughout life. Services for individuals with autism and their families vary widely, but in most European countries, provision is limited. In 2018, European Society of Child and Adolescent Psychiatry (ESCAP) identified the need for a Practice Guidance document that would help to improve knowledge and practice, especially for individuals in underserviced areas. The present document, prepared by the ASD Working Party and endorsed by the ESCAP Board on October 3, 2019, summarises current information on autism and focuses on ways of detecting, diagnosing, and treating this condition.

Truncating variant burden in high-functioning autism and pleiotropic effects of LRP1 across psychiatric phenotypes

Background: Previous research has implicated de novo and inherited truncating mutations in autism-spectrum disorder. We aim to investigate whether the load of inherited truncating mutations contributes similarly to high-functioning autism, and to characterize genes that harbour de novo variants in high-functioning autism. Methods: We performed whole-exome sequencing in 20 high-functioning autism families (average IQ = 100). Results: We observed no difference in the number of transmitted versus nontransmitted truncating alleles for high-functioning autism (117 v. 130, p = 0.78). Transmitted truncating and de novo variants in high-functioning autism were not enriched in gene ontology (GO) or Kyoto Encyclopedia of Genes and Genomes (KEGG) categories, or in autism-related gene sets. However, in a patient with high-functioning autism we identified a de novo variant in a canonical splice site of LRP1, a postsynaptic density gene that is a target for fragile X mental retardation protein (FRMP). This de novo variant leads to in-frame skipping of exon 29, removing 2 of 6 blades of the ß-propeller domain 4 of LRP1, with putative functional consequences. Large data sets implicate LRP1 across a number of psychiatric disorders: de novo variants are associated with autism-spectrum disorder (p = 0.039) and schizophrenia (p = 0.008) from combined sequencing projects; common variants using genome-wide association study data sets from the Psychiatric Genomics Consortium show gene-based association in schizophrenia (p = 6.6 × E−07) and in a meta-analysis across 7 psychiatric disorders (p = 2.3 × E−03); and the burden of ultra-rare pathogenic variants has been shown to be higher in autism-spectrum disorder (p = 1.2 × E−05), using whole-exome sequencing from 6135 patients with schizophrenia, 1778 patients with autism-spectrum disorder and 7875 controls. Limitations: We had a limited sample of patients with high-functioning autism, related to difficulty in recruiting probands with high cognitive performance and no family history of psychiatric disorders. Conclusion: Previous studies and ours suggest an effect of truncating mutations restricted to severe autism-spectrum disorder phenotypes that are associated with intellectual disability. We provide evidence for pleiotropic effects of common and rare variants in the LRP1 gene across psychiatric phenotypes.

[Functional adaptation and disorders of the autistic spectrum]. / Adaptación funcional y trastornos del espectro autista.

Autism spectrum disorders (ASD) are neurodevelopmental disorders that affect social communication and present stereotyped behaviors; 30% of the cases diagnosed with ASD have intellectual disability and 2/3 an intellectual capacity within the norm. Although cognitive ability is related to better functional adaptation, however, the vast majority of people with ASD in adulthood have limited autonomy and are dependent on adults. In this article we review the concept of functional adaptation, its relationship with ASD, factors that influence a better functional adaptation, how to evaluate it and implications for treatment. Functional adaptation in ASD is an essential concept, related to prognosis. The knowledge of the factors involved in the functional adaptation and its measure will facilitate the incorporation of very relevant aspects for treatment.

Los trastornos del espectro autista (TEA) son trastornos del neurodesarrollo que afectan la comunicación social y presentan conductas estereotipadas. Un 30% de los casos diagnosticados con TEA tienen discapacidad intelectual y 2/3 una capacidad intelectual dentro de la norma. Aunque la capacidad cognitiva esta relacionada con una mejor adaptación funcional, sin embargo la gran mayoría de las personas con TEA en edad adulta tienen una limitada autonomía y son dependientes de los adultos. En este artículo se revisa el concepto de adaptación funcional, su relación con el TEA, factores que influyen en una mejor adaptación funcional, como evaluarla y implicaciones para el tratamiento. La adaptación funcional en TEA es un concepto esencial, relacionado con el pronóstico. El conocimiento de los factores implicados en la adaptación funcional y la medida de ellas, facilita la incorporación de aspectos muy relevantes en el tratamiento.

Long-term far-transfer effects of working memory training in children with ADHD: a randomized controlled trial.

ADHD affects working memory (WM) and other executive functions (EFs) and thereby negatively impacts school performance, clinical symptoms and functional impairment. The main aim of this study was to analyse the efficacy of computerized WM training (CWMT) on EF rating scales. A secondary objective was to assess its efficacy on performance-based measures of EF (PBMEF), learning, clinical symptoms and functional impairment. 66 children with combined-type ADHD between 7 and 12 years of age from the Child and Adolescent Psychiatric Unit (Spain) were included in this randomized, double-blind, placebo-controlled, parallel-group clinical trial. The participants were randomized (1:1) to an experimental group (EG) (CWMT) (n = 36) or a control group (CG) (placebo training). Assessments were conducted at baseline (T0), 1-2 weeks (T1), and 6 months post-intervention (T2) with the administration of EF rating scales, PBMEF, measures of academic achievement, and questionnaires regarding clinical symptoms and functional impairment. Participants, parents, teachers and professionals who performed the cognitive assessments were blinded. Adjusted multiple linear regression analysis showed significant improvements in EF scales-parent version, from T1 to T2, on the metacognition index [p = 0.03, d' = -0.78 (95 % CI -1.28 to -0.27)] and on WM (also significant at T2-T0) and plan/organize subscales. Significant improvements were also noted in EF scales-teacher version, from T0 to T1 and T2, on the metacognitive index [p = 0.05, d' = -0.37 (95 % CI -0.86 to 0.12) T1-T0, p = 0.02, d' = -0.81 (95 % CI -1.31 to -0.30) T2-T0] and on the initiate, WM, monitor and shift subscales. There were also significant improvements in PBMEF, ADHD symptoms, and functional impairment. CWMT had a significant impact on ADHD deficits by achieving long-term far-transfer effects.

Delphi Consensus on Attention Deficit Hyperactivity Disorder (ADHD): evaluation by a panel of experts.

INTRODUCTION: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in childhood, which is frequently maintained in adolescent and adult age. It presents great clinical heterogeneity, significantly affecting the functioning of those who suffer it. Although drug treatments obtain results by themselves, the approach should be multidisciplinary and be adapted to the specific needs of each patient and his/ her family. Given the variety of drugs currently available to treat ADHD, there are diverse opinions on the most effective way to approach this disorder. The objective of this work is to study the opinion of an expert clinical panel and to know the professional criteria used to define key concepts and therapeutic guidelines of ADHD in Spain. METHODOLOGY: The project was carried out in four phases: 1) Constitution of a Scientific Committee, responsible for the preliminary biographic review and the formulation of the questionnaire; 2) selection of an expert panel of specialists with special interest and/or experience in the treatment of ADHD; 3) Likert type structured survey (online platform) in two rounds with interim processing of opinions; and 4) collection and final analysis of results. RESULTS: The experts’ panel achieved a consensus in 55 of the 58 items making up the questionnaire, finding 3 items in which sufficient unanimity of criteria was not achieved because of the high number of experts were found in positions of non-certainty. CONCLUSIONS: Overall, the experts of this study reached a high level of agreement in the criteria proposed in the survey, which could be generalized as indications for the clinical practice in the management of ADHD. Similarly, and given the dispersion of the results in some of the items and the lack of consensus in others, some points remain as object of discussion.

Daily life impairments associated with childhood/adolescent attention-deficit/hyperactivity disorder as recalled by adults: results from the European Lifetime Impairment Survey.

INTRODUCTION: The Lifetime Impairment Survey, conducted in Europe, assessed impairment and symptoms of attention-deficit/hyperactivity disorder (ADHD) in childhood, and experiences of ADHD diagnosis and treatment, as recalled by adults. METHODS: Adults with ADHD and without ADHD (control group) were invited to participate in an internet-based survey and report on their childhood experiences. History of ADHD diagnosis was self-reported. Groups were compared using impairment and symptom scales. RESULTS: Overall, 588 adults with ADHD and 736 without ADHD participated. Mean (standard deviation [SD]) age at diagnosis of ADHD was 20.0 (12.6) years (median 18.0) following consultation with 3.8 (5.1) doctors (median 2) over 44.6 (69.3) months (median 17.0). A total of 64.1% (377/588) of adults with ADHD reported frustration or difficulties during the diagnostic process. The ADHD group had a higher mean (SD) score versus control for general (3.3 [1.2] vs 2.1 [1.2]; p < 0.001) and school impairment (2.8 [0.7] vs 2.3 [0.6]; p < 0.001) but not home impairment (2.1 [0.5] for both groups). Discussion The survey demonstrated that ADHD had a negative impact on all aspects of childhood investigated, as recalled by adults. CONCLUSIONS: These data provide insights into childhood impairments and identify areas for improvement in the management and treatment of ADHD.

Expert recommendation: contributions to clinical practice of the new prodrug lisdexamfetamine dimesylate (LDX) in the treatment of attention deficit hyperactivity disorder (ADHD).

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurobiological disorders in childhood, and is characterized by inappropriate levels of inattention, hyperactivity and/or impulsiveness, with an estimated prevalence of 5.29%. ADHD can have a negative impact upon all areas of the life of the patient. The main clinical guides accept multimodal treatment, involving both pharmacological and psychological measures, as the best management approach in ADHD (psychoeducational, behavioural and academic). Lisdexamfetamine dimesylate (LDX) is a new drug for the treatment of ADHD. A multidiscipline expert document has been developed, compiling the scientific evidence referred to this new molecule. The study also addresses the existing shortcomings in current drug therapy for ADHD and the contributions of LDX to routine clinical practice, in an attempt to help and guide physicians in the use of this new treatment. This document is endorsed by the ADHD and Psychoeducational Development task Group of the Spanish Society of Primary Care Pediatrics (Grupo de TDAH y Desarrollo Psicoeducativo de la Asociación Española de Pediatría de Atención Primaria, AEPap), the Spanish Society of Pediatric Neurology (Sociedad Española de Neurología Pediátrica, SENEP) and the Spanish Society of Out-hospital Pediatrics and Primary Care (Sociedad Española de Pediatría Extrahospitalaria y Atención Primaria, SEPEAP).

[Autistic spectrum disorders, attention deficit disorders, hyperactivity and emotional dysregulation: masking and approach]. / Trastornos del espectro autista, trastornos por déficit de atención hiperactividad y desregulación emocional: enmascaramiento y abordaje.

Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorders (ADHD) are Neurodevelopmental Disorders (ND) that frequently coexist together and have etiological, biological, and clinical factors in common. The comorbidity of both neurodevelopmental disorders is associated with a delay or lack of ASD diagnosis and the development of perceptual, emotional, cognitive and behavioral alterations related to Emotional Dysregulation (ED) is common. When both TN are not diagnosed in childhood, they frequently receive wrong diagnoses at later ages, the most frequent being Borderline Personality Disorder (BPD). The clinical presentation of the association of ASD and ADHD, the association with ED, differentiation of BPD, and evaluation and intervention are here analyzed. The comorbidity ASD, ADHD, ED is a more severe disorder associated to polypharmacology and hospital admissions.

Los Trastornos del Espectro Autista (TEA) y los Trastornos por Déficit de Atención Hiperactividad (TDAH) son Trastornos del Neurodesarrollo (TN) que coexisten frecuentemente y que tienen factores etiológicos, biológicos, clínicos en común. La comorbilidad de ambos TN se asocia a un retraso en el diagnóstico del TEA o un diagnóstico que nunca llegan a recibir y es frecuente el desarrollo de alteraciones perceptivas, emocionales, cognitivas y conductuales relacionadas con la Desregulación Emocional (DE). Cuando ambos TN no son diagnosticados en infancia, frecuentemente reciben diagnósticos equivocados en edades más tardías, siendo el más frecuente el Trastorno Límite de Personalidad (TLP). Se analiza la presentación clínica de la asociación del TEA y el TDAH, la asociación con DE, diferenciación del TLP y evaluación e intervención. La comorbilidad TEA, TDAH, DE, es un trastorno más severo, asociado a poli farmacología y a ingresos hospitalarios.

Reduced stereotypicality and spared use of facial expression predictions for social evaluation in autism.

Background/Objective: Autism has been investigated through traditional emotion recognition paradigms, merely investigating accuracy, thereby constraining how potential differences across autistic and control individuals may be observed, identified, and described. Moreover, the use of emotional facial expression information for social functioning in autism is of relevance to provide a deeper understanding of the condition. Method: Adult autistic individuals (n = 34) and adult control individuals (n = 34) were assessed with a social perception behavioral paradigm exploring facial expression predictions and their impact on social evaluation. Results: Autistic individuals held less stereotypical predictions than controls. Importantly, despite such differences in predictions, the use of such predictions for social evaluation did not differ significantly between groups, as autistic individuals relied on their predictions to evaluate others to the same extent as controls. Conclusions: These results help to understand how autistic individuals perceive social stimuli and evaluate others, revealing a deviation from stereotypicality beyond which social evaluation strategies may be intact.

[Autism and depression: clinical presentation, evaluation and treatment]. / Autismo y depresión: presentación clínica, evaluación y tratamiento.

the social and communication development and present a restricted and stereotyped pattern of interests and conduct. The depression associated to autism present infra detection and is associated to an increase of suicidal ideation, self-harming and suicide. Objective: to analyze the characteristics of autism and depression when coexist and based on the few available evidence, to make recommendations on evaluation and treatment. The existing evidence of autism associated with depression, its epidemiology, risk factors, evaluation instruments and treatment is presented. Conclusions: The autism associated to depression presents own characteristics, related to infra detection, infra treatment, worse response to treatment and evolution.

Introducción: El autismo o los Trastornos del Espectro Autista (TEA) son alteraciones del neurodesarrollo que afectan el desarrollo socio comunicativo, y presentan un patrón restringido y estereotipado de intereses y conducta. La depresión asociada al autismo esta infra detectada y se asocia a un aumento de ideación suicida, autolesiones y suicido Objetivo: analizar las características del autismo y de la depresión cuando coexisten y en base a la escasa evidencia disponible, realizar recomendaciones en la evaluación y tratamiento. Se presenta la evidencia existente del autismo asociado a la depresión, su epidemiología, factores de riesgo, instrumentos de evaluación y recomendaciones en su intervención. Conclusiones: El autismo asociado a depresión presenta características propias, relacionadas con infra detección diagnóstica, infra tratamiento, peor respuesta a tratamiento y peor evolución.

Review of pharmacogenomics of psychiatric comorbidities in autism spectrum disorder.

Approximately 70% of individuals diagnosed with autism spectrum disorder (ASD) receive at least one psychotropic medication to treat comorbidities. However, the response to treatment with these drugs is far from satisfactory, with 30-50% of treated patients not responding adequately or developing severe and long-lasting side effects. There is strong evidence of the clinical utility of pharmacogenetics for the personalization of antipsychotic and antidepressant treatments in adult populations. However, the use of pharmacogenetic interventions for the personalization of treatment in ASD populations is minimal. The aim of this review is to summarize the findings of pharmacogenetic studies conducted in subjects with ASD and illustrate their utility in the personalization of treatment with psychoactive drugs in this population group.

Prevalence, comorbidities, and profiles of neurodevelopmental disorders according to the DSM-5-TR in children aged 6 years old in a European region.

Background: There are no studies that measure the prevalence and real comorbidities of neurodevelopmental disorders (NDDs) according to the DSM-5-TR in 6-year-old children in population and clinical samples or studies that measure them as a whole. The data on the prevalence of these disorders are usually disparate because of the estimation methods (direct/indirect), the type of sample (population/clinical/school), and the ages studied. Methods: The initial sample (289 subjects) was representative of 6-year-old children in the entire population of Menorca, obtained from pediatric primary care services (100% of the sample). The patients were divided into two groups based on the criterion of verification of clinical warning signs. One of the groups represented the clinical or experimental sample (EG) (81 subjects) at risk of NDDs; the other group was considered the control sample (CG) (210 subjects), and they were subjects without risk of suffering NDDs. A direct clinical assessment of the clinical sample was carried out, and they were administered the Wechsler Intelligence Scale for Children (WISC-V), the Clinical Evaluation of Language Fundamentals (CELF-5), the Battery for the evaluation of the processes of revised reading (Batería para la evaluación de los procesos de lectura revisada - PROLEC-R), the Test for the Diagnosis of Basic Mathematical Competences, (TEDI-MATH), and the Developmental Coordination Disorder Questionnaire (DCDQ). Results: A total of 21.5% of the initial sample suffered from an NDD. A total of 2.4% presented autism spectrum disorder (ASD); 14% presented attention-deficit hyperactivity disorder (ADHD); 0.34% presented mild intellectual disability; 9.54% presented communication disorder (CD) (5.8% language disorder, 3.4% phonological disorder, and 0.34% stuttering); 10% presented learning disorder with reading difficulties; 5.8% presented learning disorder with difficulties in writing; 3.11% presented learning disorder with difficulties in mathematics; 1% presented transitory tic disorder; 0.34% presented chronic tic disorder; 1% presented Tourette syndrome; 2% presented motor coordination disorder (MCD); and 0.34% presented stereotypic movement disorders. Male children were more affected than female children in general, with male/female ORs of 0.14/0.92 for the presence of comorbidities, 0.11/0.88 for combined ADHD, 0.06/0.87 for language disorder, 1.02/1.27 for MCD, and 1.39/1.02 for inattentive ADHD. Conclusion: In disadvantaged contexts, there was a higher prevalence of NDDs and comorbidities, unless the disorder was extreme, in which case only the NDD manifestations were presented. A significant proportion of the sample had not been previously diagnosed (88.6%); therefore, early detection programs are recommended to identify warning signs and develop policies that help and support the most disadvantaged sectors of the population.

Linking heart rate variability to psychological health and brain structure in adolescents with and without conduct disorder.

Aims: Heart rate variability (HRV) measures have been suggested in healthy individuals as a potential index of self-regulation skills, which include both cognitive and emotion regulation aspects. Studies in patients with a range of psychiatric disorders have however mostly focused on the potential association between abnormally low HRV at rest and specifically emotion regulation difficulties. Emotion regulation deficits have been reported in patients with Conduct Disorder (CD) however, the association between these emotion regulation deficits and HRV measures has yet to be fully understood. This study investigates (i) the specificity of the association between HRV and emotion regulation skills in adolescents with and without CD and (ii) the association between HRV and grey matter brain volumes in key areas of the central autonomic network which are involved in self-regulation processes, such as insula, lateral/medial prefrontal cortices or amygdala. Methods: Respiratory sinus arrhythmia (RSA) measures of HRV were collected from adolescents aged between 9-18 years (693 CD (427F)/753 typically developing youth (TD) (500F)), as part of a European multi-site project (FemNAT-CD). The Inverse Efficiency Score, a speed-accuracy trade-off measure, was calculated to assess emotion and cognitive regulation abilities during an Emotional Go/NoGo task. The association between RSA and task performance was tested using multilevel regression models. T1-weighted structural MRI data were included for a subset of 577 participants (257 CD (125F); 320 TD (186F)). The CerebroMatic toolbox was used to create customised Tissue Probability Maps and DARTEL templates, and CAT12 to segment brain images, followed by a 2 × 2 (sex × group) full factorial ANOVA with RSA as regressor of interest. Results: There were no significant associations between RSA and task performance, neither during emotion regulation nor during cognitive regulation trials. RSA was however positively correlated with regional grey matter volume in the left insula (pFWE = 0.011) across all subjects. Conclusion: RSA was related to increased grey matter volume in the left insula across all subjects. Our results thus suggest that low RSA at rest might be a contributing or predisposing factor for potential self-regulation difficulties. Given the insula's role in both emotional and cognitive regulation processes, these brain structural differences might impact either of those.

Action initiation and punishment learning differ from childhood to adolescence while reward learning remains stable.

Theoretical and empirical accounts suggest that adolescence is associated with heightened reward learning and impulsivity. Experimental tasks and computational models that can dissociate reward learning from the tendency to initiate actions impulsively (action initiation bias) are thus critical to characterise the mechanisms that drive developmental differences. However, existing work has rarely quantified both learning ability and action initiation, or it has relied on small samples. Here, using computational modelling of a learning task collected from a large sample (N = 742, 9-18 years, 11 countries), we test differences in reward and punishment learning and action initiation from childhood to adolescence. Computational modelling reveals that whilst punishment learning rates increase with age, reward learning remains stable. In parallel, action initiation biases decrease with age. Results are similar when considering pubertal stage instead of chronological age. We conclude that heightened reward responsivity in adolescence can reflect differences in action initiation rather than enhanced reward learning.